Investigating the role of neighborhood socioeconomic status and germline genetics on prostate cancer risk.

Genetic factors play an important role in prostate cancer (PCa) development with polygenic risk scores (PRS) predicting disease risk across genetic ancestries. However, there are few convincing modifiable factors for PCa and little is known about their potential interaction with genetic risk. Our study explores the role of neighborhood socioeconomic status (nSES)-and how it may interact with PRS-on PCa risk. We analyzed incident PCa cases and controls of European (cases = 5,960; controls = 93,990) and African (cases = 109; controls = 1,226) ancestry from the UK Biobank cohort. Using the English indices of deprivation, a set of validated metrics that quantify lack of resources within geographical areas, we performed logistic regression to investigate the main effects and interactions between nSES deprivation and genetic susceptibility to PCa, represented by a multi-ancestry PRS comprised of 269 genetic variants. The PRS was associated with PCa in the European (OR = 2.04; 95% confidence interval [CI], 2.00-2.09; p = 5.34 × 10^-807) and African (OR = 1.35; 95% CI, 1.16-1.58; p = 1.05 × 10^-4) ancestries. Additionally, nSES deprivation indices were inversely associated with PCa: employment, education, health, and income. From this, we suspect that PRS, through biological mechanisms, and nSES deprivation, likely through differences in screening, are associated with PCa, but act independently of each other. Our findings suggest that genetic factors and social determinants of health measured by neighborhood socioeconomic status do not synergistically increase risk of PCa.